Phospholipase A2 structure/function, mechanism, and signaling

Burke, John E.; Dennis, Edward A.

doi:10.1194/jlr.r800033-jlr200

Cited by 758 publications

(632 citation statements)

References 64 publications

(65 reference statements)

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“…AA is released from the sn-2 position of membrane phospholipids by several phospholipases A 2 (PLA 2 ), a large protein family that includes secreted as well as cytosolic and membrane-associated enzymes (Burke and Dennis, 2009). Neuronal cells express at least 2 types of phospholipases A 2 : (1) the calcium-independent membrane-associated enzyme (iPLA 2 ) that is thought to be involved in the metabolism of docosahexaenoic acid, the major n-3 long-chain polyunsaturated fatty acid in the brain; and (2) the calciumdependent cytosolic enzyme (cPLA 2 ) that displays a strong selectivity for the AA-containing phospholipids (for review, see Sun et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit

Desbène

Malaplate-Armand

Youssef

et al. 2012

Neurobiology of Aging

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Soluble beta-amyloid (A␤) oligomers are considered to putatively play a critical role in the early synapse loss and cognitive impairment observed in Alzheimer's disease. We previously demonstrated that A␤ oligomers activate cytosolic phospholipase A 2 (cPLA 2 ), which specifically releases arachidonic acid from membrane phospholipids. We here observed that cPLA 2 gene inactivation prevented the alterations of cognitive abilities and the reduction of hippocampal synaptic markers levels noticed upon a single intracerebroventricular injection of A␤ oligomers in wild type mice. We further demonstrated that the A␤ oligomer-induced sphingomyelinase activation was suppressed and that phosphorylation of Akt/protein kinase B (PKB) was preserved in neuronal cells isolated from cPLA 2 Ϫ/Ϫ mice. Interestingly, expression of the A␤ precursor protein (APP) was reduced in hippocampus homogenates and neuronal cells from cPLA 2 Ϫ/Ϫ mice, but the relationship with the resistance of these mice to the A␤ oligomer toxicity requires further investigation. These results therefore show that cPLA 2 plays a key role in the A␤ oligomer-associated neurodegeneration, and as such represents a potential therapeutic target for the treatment of Alzheimer's disease.

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Section: Introductionmentioning

confidence: 99%

Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit

Desbène

Malaplate-Armand

Youssef

et al. 2012

Neurobiology of Aging

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“…Moreover, many reports have demonstrated multiple levels of cross-talk between PLA2 and calcium, and in the majority of cases, an increase in cytoplasmic calcium is required for the increase in PLA2 activity (37). In contrast, two products of PLA2, LPA and AA, have been shown to trigger the release of calcium from the ER (via LPA receptors) and the influx of extracellular calcium (via the arachidonate-regulated calcium channel), respectively (38, 39).…”

Section: Noxa Is Required For Gossypol-mediated Sensitization Tomentioning

confidence: 99%

“…The PLA2 family of enzymes contains many members, which can be divided into 14 different groups based on functional similarity (37). The expression levels of these different groups vary greatly among species and cell type.…”

Section: Noxa Is Required For Gossypol-mediated Sensitization Tomentioning

confidence: 99%

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Soderquist¹,

Danilov

Eastman

2014

Journal of Biological Chemistry

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Background:The mechanism through which gossypol mediates anti-cancer activity is poorly understood. Results: Gossypol rapidly activates phospholipase A2, increases cytoplasmic calcium, endoplasmic reticulum stress, and NOXA, and sensitizes cells to apoptosis. Conclusion: Phospholipase A2 is a novel target of gossypol. Significance: This pathway can explain many reported activities of gossypol including sensitization to the BCL2 inhibitor,

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“…AACOCF3 has been reported to inhibit both cPLA2 and iPLA2, but not sPLA2 [18,19]. AACOCF3 did not cause significant, dose-dependent inhibition of HASMC chemotaxis to PDGF BB from 0.5 µM to 50 µM concentration ( Figure 3A).…”

Section: Resultsmentioning

confidence: 93%

“…The direct products of PLA2 action, lysophospholipids and fatty acids, can themselves act as cellular mediators or serve as precursors for the formation of mediators such as platelet-activating factor and eicosanoids [17,18]. Phospholipase A2 specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing fatty acid and lysophospholipid [19].…”

Section: Introductionmentioning

confidence: 99%

Cytosolic Phospholipase A2 Alpha is Required for Human Smooth Muscle Cell Proliferation and Not Migration to Platelet Derived Growth Factor BB

Haghayeghi¹,

Jt²,

Pandurovic³

et al. 2017

J Cell Signal

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Platelet derived growth factor BB (PDGF BB) has an important influence on smooth muscle cell migration and proliferation in restenosis and atherosclerosis. Our understanding of different signal transduction pathways involved in the response of smooth muscle cells to PDGF BB is potentially significant for understanding and manipulating these processes. Prior studies have demonstrated a crucial activation of cytosolic phospholipase A2 (cPLA2) in smooth muscle cells to PDGF BB with the production of arachidonic acid and prostaglandin E2. In this study, we first investigated the role of cPLA2α on human aortic smooth muscle cell (HASMC) migration using modified Boyden chamber assay and under agarose migration studies. AACOCF3 (cPLA2 and iPLA2 inhibitor), 1,2,4-trisubstituted pyrrolidine derivative (cPLA2 inhibitor), and Bromoenol lactone (iPLA2 inhibitor) had no effect on HASMC chemotaxis to PDGF-BB in a modified Boyden chamber. These results were confirmed with specific inhibition of cPLA2α using small interfering RNA (siRNA) showing that HASMC migration was not inhibited in modified Boyden chamber or under agarose migration studies. Using the same siRNA to cPLA2 alpha had very significant inhibition to PDGF-BB dependent HASMC proliferation. These data demonstrate there is a distinct role especially for cPLA2α on human aortic HASMC proliferation and not migration to PDGF-BB.

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Phospholipase A2 structure/function, mechanism, and signaling

Cited by 758 publications

References 64 publications

Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit

Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Cytosolic Phospholipase A2 Alpha is Required for Human Smooth Muscle Cell Proliferation and Not Migration to Platelet Derived Growth Factor BB

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